Aspirin induces oncosis in tumor cells

In contrast to the well-known anti-tumor mechanisms of aspirin in inducing apoptosis or autophagy, we here for the first time report oncosis induced by aspirin in tumor cells. In vitro and in vivo analysis showed that aspirin induced compromised Bcl-XL level and subsequent ATP depletion. Overexpression of CFP-Bcl-XL in Hela and A549 cells observably inhibited aspirin-induced ATP depletion and almost completely inhibited the aspirin-induced cells bubbling, while pharmacological inhibition of endogenous Bcl-XL activity by ABT-737 remarkably promoted aspirin-induced ATP depletion and cells bubbling, suggesting the key inhibitory role of Bcl-XL in aspirin-induced oncosis. Overexpression of Bax/Bad significantly promoted aspirin-induced oncosis. In addition, cells cultured in a glucose-free medium with low ATP level exhibited higher percentage of bubbling cells than the cells cultured in a glucose medium with high ATP level under aspirin treatment, indicating the important role of ATP depletion in aspirin-induced oncosis. Furthermore, caspase-3 was demonstrated to be not involved in aspirin-induced oncosis. Animal studies showed that aspirin treatment significantly inhibited tumors growth, but did not induce toxicities to mice. Collectively, aspirin inhibits tumors growth in mice and induces oncosis in which the compromised Bcl-XL and intracellular ATP depletion play a dominant role, which provides insights into the therapeutic strategy of aspirin in oncology.